This project is a continuation from last year. Its aim is to test in rhesus macaques the potency of various live vectors carrying human immunodeficiency virus type 1 (HIV-1), HIV-2 and simian immunodeficiency virus (SIV) antigens in eliciting a protective immunoresponse. Three different delivery systems have been tested: 1) attenuated vaccinia, 2) avipox, and 3) attenuated Salmonella typhimurium strain as a bacterial vaccine, carrying HIV/SIV antigens. The immunoresponse in the immunized animals was further stimulated by using purified viral antigens (either native or recombinant viral subunits). Rhesus macaques, which are susceptible to the infection of both SIV(mac251) and HIV-2, were used. The end point of these studies was the protection from infection by either SIV251 or HIV-2. Vectors containing HIV-1 antigens were also evaluated for their immunogenicity in rhesus macaques. The animals immunized with SIV/HIV-2 and HIV-1 recombinant vectors were challenged twice with live HIV-2 virus six months apart. The results indicated that NYVAC recombinant vaccines are better immunogens than ALVAC and recombinant Salmonella and provide long lasting protection without need of further boosts. The second part of this project involved the development of a human T- cell leukemia/lymphotropic virus type 1 (HTLV-I) vaccine. NYVAC and ALVAC HTLV-I constructs expressing the HTLV-I envelope were used to immunize rabbits. Testing of the immunoresponse against these constructs in the immunized animals with parallel analysis on the natural immunoresponse in humans is ongoing and preliminary results suggest that protection against a cell-associated HTLV-I challenge can be achieved.